Pharmacokinetics and safety of penciclovir following oral administration of famciclovir to cats

To investigate penciclovir pharmacokinetics following single and multiple oral administrations of famciclovir to cats. 8 adult cats. A balanced crossover design was used. Phase I consisted of a single administration (62.5 mg, PO) of famciclovir. Phase II consisted of multiple doses of famciclovir (6...

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Bibliographic Details
Published in:	American journal of veterinary research Vol. 68; no. 11; pp. 1252 - 1258
Main Authors:	Thomasy, S.M, Maggs, D.J, Moulin, N.K, Stanley, S.D
Format:	Journal Article
Language:	English
Published:	United States 01-11-2007
Subjects:	2-Aminopurine - analogs & derivatives 2-Aminopurine - pharmacology Acyclovir - analogs & derivatives Acyclovir - blood Acyclovir - pharmacokinetics Administration, Oral adverse effects Animals antiviral agents Antiviral Agents - blood Antiviral Agents - pharmacokinetics Antiviral Agents - pharmacology antiviral properties Area Under Curve cat diseases cats Cats - blood Cats - metabolism combination drug therapy Cross-Over Studies dosage dose response Drug Interactions drug safety famciclovir Felid herpesvirus 1 Female Half-Life oral administration penciclovir pharmacokinetics Prodrugs - pharmacology Specific Pathogen-Free Organisms viral diseases of animals and humans
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Summary:	To investigate penciclovir pharmacokinetics following single and multiple oral administrations of famciclovir to cats. 8 adult cats. A balanced crossover design was used. Phase I consisted of a single administration (62.5 mg, PO) of famciclovir. Phase II consisted of multiple doses of famciclovir (62.5 mg, PO) given every 8 or 12 hours for 3 days. Plasma penciclovir concentrations were assayed via liquid chromatography-mass spectrometry at fixed time points after famciclovir administration. Following a single dose of famciclovir, the dose-normalized (15 mg/kg) maximum concentration (C(max)) of penciclovir (350 +/- 180 ng/mL) occurred at 4.6 +/- 1.8 hours and mean +/- SD apparent elimination half-life was 3.1 +/- 0.9 hours. However, the dose-normalized area under the plasma penciclovir concentration-time curve extrapolated to infinity (AUC(0-->)) during phase I decreased with increasing dose, suggesting either nonlinear pharmacokinetics or interindividual variability among cats. Accumulation occurred following multiple doses of famciclovir administered every 8 hours as indicated by a significantly increased dose-normalized AUC, compared with AUC(0-->) from phase 1. Dose-normalized penciclovir C(max)following administration of famciclovir every 12 or 8 hours (290 +/- 150 ng/mL or 780 +/- 250 ng/mL, respectively) was notably less than the in vitro concentration (3,500 ng/mL) required for activity against feline herpesvirus-1. Penciclovir pharmacokinetics following oral famciclovir administration in cats appeared complex within the dosage range studied. Famciclovir dosages of 15 mg/kg administered every 8 hours to cats are unlikely to result in plasma penciclovir concentrations with activity against feline herpesvirus-1.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0002-9645 1943-5681
DOI:	10.2460/ajvr.68.11.1252